Targeting Post-Translational Modifications to Improve Combinatorial Therapies in Breast Cancer: The Role of Fucosylation

Various tumors rely on post-translational modifications (PTMs) to promote invasiveness and angiogenesis and to reprogram cellular energetics to abate anti-cancer immunity. Among PTMs, fucosylation is a particular type of glycosylation that has been linked to different aspects of immune and hormonal physiological functions as well as hijacked by many types of tumors. Multiple tumors, including breast cancer, have been linked to dismal prognoses and increased metastatic potential due to fucosylation of the glycan core, namely core-fucosylation. Pre-clinical studies have examined the molecular mechanisms regulating core-fucosylation in breast cancer models, its negative prognostic value across multiple disease stages, and the activity of in vivo pharmacological inhibition, instructing combinatorial therapies and translation into clinical practice. Throughout this review, we describe the role of fucosylation in solid tumors, with a particular focus on breast cancer, as well as physiologic conditions on the immune system and hormones, providing a view into its potential as a biomarker for predicating or predicting cancer outcomes, as well as a potential clinical actionability as a biomarker.